Ammonium Chloride → (S)-1-[2-(2-bromo-5-methoxy-4-methyl-phenyl)-acetyl]-2-(4-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one

HRID 1691782Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:13][C:12](=[O:14])[CH:11]=[CH:10][NH:9]2)=[CH:4][CH:3]=1.C([Li])CCC.[Br:20][C:21]1[CH:26]=[C:25]([CH3:27])[C:24]([O:28][CH3:29])=[CH:23][C:22]=1[CH2:30][C:31](Cl)=[O:32].[Cl-].[NH4+]>C1COCC1>[Br:20][C:21]1[CH:26]=[C:25]([CH3:27])[C:24]([O:28][CH3:29])=[CH:23][C:22]=1[CH2:30][C:31]([N:9]1[CH:10]=[CH:11][C:12](=[O:14])[CH2:13][C@H:8]1[C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)=[O:32]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of (S)-2-(4-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one (80 mg) in THF (1.5 mL) at −78° C. under argon was added n-butyllithium (0.184 mL, 2.5M in hexanes). After ten minutes a solution of (2-bromo-5-methoxy-4-methyl-phenyl)-acetic acid chloride (116 mg) in THF (1 mL) was added. The mixture was stirred at −78° C. for 30 minutes, then at room temperature for 30 minutes. Saturated aqueous ammonium chloride was added and the mixture was extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (Na2SO4), filtered and concentrated to dryness under reduced pressure. Purification of the residue by flash chromatography (hexanes/ethyl acetate gradient) gave (S)-1-[2-(2-bromo-5-methoxy-4-methyl-phenyl)-acetyl]-2-(4-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one as a foam. MS (M+H) 433.

Workup

waitat room temperature for 30 minutes
extractionthe mixture was extracted with ethyl acetate
washThe combined organic extracts were washed with brine
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated to dryness under reduced pressure
customPurification of the residue by flash chromatography (hexanes/ethyl acetate gradient)

Sources & evidence

ORD record: ord-31e9837716044988a13be9915aea90a6
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08153808B2

Reaction notes

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